NLR family pyrin domain-containing protein 3 (NLRP3)

NLR family pyrin domain-containing protein 3 (NLRP3) is a cytosolic pattern recognition receptor that acts as a key sensor within the innate immune system. Upon detection of diverse danger signals—including microbial infection, cellular damage, ionic fluxes, mitochondrial dysfunction, and lysosomal rupture—NLRP3 assembles into the multiprotein NLRP3 inflammasome complex. This complex recruits the adaptor ASC and pro-caspase-1 to facilitate caspase-1 activation. Activated caspase-1 then processes pro-inflammatory cytokines interleukin 1 beta (IL-1β) and interleukin 18 (IL-18), as well as gasdermin D to induce pyroptosis—a form of inflammatory cell death. Dysregulation or hyperactivation of the NLRP3 pathway is implicated in numerous diseases characterized by chronic inflammation such as autoimmune disorders, metabolic syndrome/type 2 diabetes, neurodegeneration including Alzheimer’s disease, cardiovascular diseases, and acute inflammatory conditions like pancreatitis. Pharmacological targeting focuses on inhibiting either upstream priming events or direct assembly/activation steps within the inflammasome pathway.

Other names

NACHT, LRR and PYD domains-containing protein 3CryopyrinCIAS1NALP3PYPAF1

Inhibition of inflammasome assembly/activation, blockade of deubiquitination required for activation, or suppression of ATPase activity or oligomerization.